ID | 66699 |
フルテキストURL | |
著者 |
Kano, Tomonori
Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Ishikawa, Kazuya
Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Furuta, Kazuyuki
Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Kaito, Chikara
Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
ORCID
Kaken ID
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抄録 | Colistin is a cationic cyclic antimicrobial peptide used as a last resort against multidrug-resistant gram-negative bacteria. To understand the factors involved in colistin susceptibility, we screened colistin-sensitive mutants from an E. coli gene-knockout library (Keio collection). The knockout of purA, whose product catalyzes the synthesis of adenylosuccinate from IMP in the de novo purine synthesis pathway, resulted in increased sensitivity to colistin. Adenylosuccinate is subsequently converted to AMP, which is phosphorylated to produce ADP, a substrate for ATP synthesis. The amount of ATP was lower in the purA-knockout mutant than that in the wild-type strain. ATP synthesis is coupled with proton transfer, and it contributes to the membrane potential. Using the membrane potential probe, 3,3′-diethyloxacarbocyanine iodide [DiOC2(3)], we found that the membrane was hyperpolarized in the purA-knockout mutant compared to that in the wild-type strain. Treatment with the proton uncoupler, carbonyl cyanide m-chlorophenyl hydrazone (CCCP), abolished the hyperpolarization and colistin sensitivity in the mutant. The purA-knockout mutant exhibited increased sensitivity to aminoglycosides, kanamycin, and gentamicin; their uptake requires a membrane potential. Therefore, the knockout of purA, an adenylosuccinate synthase, decreases ATP synthesis concurrently with membrane hyperpolarization, resulting in increased sensitivity to colistin.
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キーワード | colistin
adenylosuccinate synthase
de novo purine synthesis
membrane potential
ATP synthesis
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発行日 | 2024-02-01
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出版物タイトル |
FEMS Microbiology Letters
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巻 | 371巻
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出版者 | Oxford University Press (OUP)
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開始ページ | fnae007
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ISSN | 1574-6968
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © The Author(s) 2024.
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
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関連URL | isVersionOf https://doi.org/10.1093/femsle/fnae007
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ライセンス | https://creativecommons.org/licenses/by/4.0/
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Citation | Tomonori Kano, Kazuya Ishikawa, Kazuyuki Furuta, Chikara Kaito, Knockout of adenylosuccinate synthase purA increases susceptibility to colistin in Escherichia coli, FEMS Microbiology Letters, Volume 371, 2024, fnae007, https://doi.org/10.1093/femsle/fnae007
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助成機関名 |
Japan Society for the Promotion of Science
Takeda Science Foundation
Ichiro Kanehara Foundation
Ryobi Teien Memory Foundation
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助成番号 | 22K14892
22H02869
22K19435
23K06130
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